Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients: the Aldo-DHF randomized controlled trial

Abstract

Objectives: To evaluate associations of omega-3 fatty acid (O3-FA) blood levels with cardiometabolic risk markers, functional capacity and cardiac function/morphology in patients with heart failure with preserved ejection fraction (HFpEF).

Background: O3-FA have been linked to reduced risk for HF and associated phenotypic traits in experimental/clinical studies.

Methods: This is a cross-sectional analysis of data from the Aldo-DHF-RCT. From 422 patients, the omega-3-index (O3I = EPA + DHA) was analyzed at baseline in n = 404 using the HS-Omega-3-Index^® methodology. Patient characteristics were; 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e' 7.1 ± 1.5; median NT-proBNP 158 ng/L (IQR 82-298). Pearson's correlation coefficient and multiple linear regression analyses, using sex and age as covariates, were used to describe associations of the O3I with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline/12 months.

Results: The O3I was below (< 8%), within (8-11%), and higher (> 11%) than the target range in 374 (93%), 29 (7%), and 1 (0.2%) patients, respectively. Mean O3I was 5.7 ± 1.7%. The O3I was inversely associated with HbA1c (r = - 0.139, p = 0.006), triglycerides-to-HDL-C ratio (r = - 0.12, p = 0.017), triglycerides (r = - 0.117, p = 0.02), non-HDL-C (r = - 0.101, p = 0.044), body-mass-index (r = - 0.149, p = 0.003), waist circumference (r = - 0.121, p = 0.015), waist-to-height ratio (r = - 0.141, p = 0.005), and positively associated with submaximal aerobic capacity (r = 0.113, p = 0.023) and LVEF (r = 0.211, p < 0.001) at baseline. Higher O3I at baseline was predictive of submaximal aerobic capacity (β = 15.614, p < 0,001), maximal aerobic capacity (β = 0.399, p = 0.005) and LVEF (β = 0.698, p = 0.007) at 12 months.

Conclusions: Higher O3I was associated with a more favorable cardiometabolic risk profile and predictive of higher submaximal/maximal aerobic capacity and lower BMI/truncal adiposity in HFpEF patients. Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients. Higher O3I was associated with a more favorable cardiometabolic risk profile and aerobic capacity (left) but did not correlate with echocardiographic markers for left ventricular diastolic function or neurohumoral activation (right). An O3I-driven intervention trial might be warranted to answer the question whether O3-FA in therapeutic doses (with the target O3I 8-11%) impact on echocardiographic markers for left ventricular diastolic function and neurohumoral activation in patients with HFpEF. This figure contains modified images from Servier Medical Art ( https://smart.servier.com ) licensed by a Creative Commons Attribution 3.0 Unported License.

Keywords: Atherogenic dyslipidemia; Diastolic dysfunction; Docosahexaenoic acid; Eicosapentaenoic acid; Functional capacity; HFpEF; Heart failure; Metabolic phenotype; Omega-3 fatty acids; Omega-3 index.

Fig. 1

The distribution of the O3I in the Aldo-DHF Cohort. O3I: n 404, mean 5.65%, SD 1.676, min 2.19%, max 12.11%

Fig. 2

Scatter Plot showing correlations between the O3I and LVEF. The O3I showed a positive association with LVEF

Fig. 3

Scatter Plots showing correlations between the O3I and HbA1c (A), TAG/HDL-C ratio (B), Triglycerides (C), Non-HDL-C (D), Body Mass Index (E), WC (F) and Waist-to-height ratio (G). The Omega-3 index was inversely associated with HbA1c (A), TAG/HDL-C ratio (B), Triglycerides (C), Non-HDL-C (D), BMI (E), WC (F) and WHtR (G)

Fig. 4

Scatter Plots showing correlations between the O3I and distance covered during the 6 MWT (A) and Maximal Diastolic BP during the 6MWT (B). The O3I showed a positive association with submaximal aerobic capacity (A) and was inversely associated with maximal diastolic BP during the 6MWT (B)